The objectives of this proposal are to continue to describe epidemiologically the natural history of non-insulin dependent diabetes mellitus (NIDDM) and its complications in tow southern Colorado counties in Hispanic- and anglo- Americans; to better understand the genetic and environmental contributions to NIDDM etiology and complications; and to elucidate risk factors that are amendable to intervention of these conditions. From 1984-1988, persons with NIDDM and representative non-diabetic controls from the community have been identified. Prospective follow-up is now underway, and this proposal seeks to continue this follow-up at two yearly intervals for 5 years on cohorts of persons with NIDDM, impaired glucose tolerance (IGT), and at four yearly intervals on normals. The specific aims include: 1) determination of the incidence of NIDDM and IGT and examination of the role of diet, physical activity, family history, and sociocultural factors (among others) for these conditions; 2) determination of the incidence of microvascular and microvascular disease endpoints, mortality, and the influence of hyperglycemia, ethnicity, and other risk factors on their incidence and prognosis; 3) determination of the frequency of polymorphic alleles at the glucose transporter, insulin receptor, apolipoprotein AI and B, and lipoprotein lipase genes and their association with risk factor and disease endpoints; 4) analysis of sex hormone levels and determination of their relationship by gender to the development of obesity, insulin resistance, IGT, NIDDM, and cardiovascular endpoints. Continued analyses of previously collected data form the prevalent and incident case-control portions of the study will also be accomplished. NIDDM constitutes a major public health problem in the United States. The San Luis Valley Diabetes Study (SLVDS) is one of only tow population-based studies of NIDDM and heart disease in Hispanics, and the only one located in a rural area. The etiology and natural history of NIDDM are still poorly understood, especially in Hispanics and Hispanics constitute the second largest minority population in the United States.